The proposed research has four Specific Aims: Specific Aim 1: To administer in each of four sensory modalities (olfaction, vision, somatosensory systems, and audition) tests that sample functions of primary sensory and modality-specific cortical areas. Specific Aim 2: To perform within-subject and group comparisons across the four sensory modalities in order to determine whether AD impairs all senses equally or differentially. Further, we shall determine whether individual subjects show the same pattern of deficit in all modalities, and whether the patterns are uniform across subjects. Specific Aim 3: To assign probability scores indicating the likelihood that a proband has familial AD (FAD) or sporadic AD (SAD), and to describe the relation between the presence, nature, and severity of sensory disorders and the probability of FAD or SAD. Specific Aim 4: To determine at autopsy the neuropathological substrates that could account for patterns of sparing and loss in sensory functions noted in the living patient. In collaboration with the Neuropathology Core of the Massachusetts Alzheimer's Disease Research Center (ADRC) we shall explore case-by-case correlations between the magnitude of specific sensory deficits and the regional and laminar neuropathological changes in each of the four sensory systems. In order to achieve these Specific Aims, we shall assess 90 AD patients, 60 elderly control subjects, and 60 young control subjects over a 3-year period, examining a range of sensory capacities in four modalities: olfaction, vision, somatosensory systems, and audition. We shall examine each sensory modality in each subject. We shall achieve a full sampling of sensory capacities by administering tests from the old and new protocols. This multidisciplinary study draws upon expertise in psychophysics, behavioral neuroscience, neurology, neuro-ophthalmology, genetic epidemiology, and neuropathology. The research takes advantage of components of the Massachusetts ADRC, including its AD patient population, Data Management Facility, and Brain Tissue Resource Center.